Overview of Amorphous Solid Dispersion Technologies

Abstract

Successful development of amorphous solid dispersion formulations depends on three primary factors: active pharmaceutical ingredient properties, stabilizing polymer, and the processing technology. Polymer provides the fundamental framework for stabilizing the amorphous form and the process supplies the energy required to transform the system into an amorphous form. This is evident from ample examples where simply physical mixing of the amorphous drug and polymer did not provide satisfactory outcome in terms of either improving the solubility or enhancing the bioavailability. Effectiveness of the process is critical to generate, capture, and preserve the amorphous form. The success of these processes is dependent on the process time and the supersaturation conditions that are being generated during the formation of the solid dispersion. From the discovery of solid dispersions in the early 1960s, the application of solid dispersion concept to solve solubility challenges in real world was limited and this was partly due to the lack of commercially viable processing technologies. However, in the past two decades this area has seen remarkable progress as the science and understanding of the manufacturing technologies, specifically spray drying and melt extrusion, have evolved considerably leading to several commercially successful amorphous products in addition to numerous in development. Besides advancing the field and scientific understanding, many technology-driven companies have thrived in this environment by enabling the development of poorly water-soluble drugs that would have otherwise been dropped from consideration. Spray drying and hot-melt extrusion have become the backbone of amorphous formulations in the pharmaceutical industry while newer technologies are constantly being added to the tool box that promise to improve quality, productivity, and/or better performance of the products. Having access to multiple technologies tremendously increases the probability of success for a large variety of compounds. The choice of technology is primarily governed by the physicochemical properties of the drug substance, availability of technology from lab scale to commercial scale, robustness of the process, product performance, and lastly the impact of the selected technology on the cost of goods.